Attachment 1 - Statement of Work Biologics.pdf

Biological Therapeutics Product Development Subject Matter Expert Consultants

STATEMENT OF WORK

PURPOSE

The purpose of this requirement is to acquire high-level subject matter expert (SME) support for translational product development at the National Institute of Neurological Disorders and Stroke (NINDS). This requirement provides support that is critical to the broad range of NINDS translational product development activities that are in-process, planned, and evolving.

BACKGROUND

The National Institutes of Health (NIH) is the nation’s leading medical research agency and the primary Federal agency whose mission is to seek fundamental knowledge about the nature and behavior of living systems and apply that knowledge to enhance health, lengthen life, reduce illness and disability, and conduct, support, and make medical discoveries that improve people’s health and save lives. The NINDS is an institute within the NIH that conducts research into the causes, treatment, and prevention of neurological disorders and stroke. The NINDS mission is to seek fundamental knowledge about the brain and nervous system and use that knowledge to reduce the burden of neurological disease.

The NINDS has a need for biological therapeutics development subject matter expert (SME) consultants to provide technical recommendations and advice that will support the translational development of novel therapeutics (Biologics) for NIH drug discovery and development programs. The support included in this contract will cover all aspects of drug discovery and development through the Phase 1 clinical trial, including but not limited to chemistry, manufacturing, and controls (CMC), assay development, pharmacokinetics and pharmacodynamics (PK/PD), absorption, distribution, metabolism, and excretion (ADME), toxicology, regulatory affairs, regulatory operations, medical writing, biostatistics, and quality assurance/quality control (QA/QC), and first-in-human trial planning and design. The NINDS is seeking vendors who can supply a broad array of Biologics subject matter experts, including all modalities and cell and gene therapies.

NIH Drug Development Programs Involving Biologics

This requirement supports the NIH Biologics development projects under the NIH Blueprint Neurotherapeutics Network Biologics (BPN-Biologics) program, the NINDS Ultra-Rare Gene Therapy (URGenT) program, the Helping to End Addiction Long-term Pain Therapeutics Development Program (HEAL-PTDP), and other extramural or intramural NIH drug discovery and development programs.

The NIH Blueprint Neurotherapeutics (BPN) network (https://neuroscienceblueprint.nih.gov/neurotherapeutics/blueprint-neurotherapeutics-bpn- network) is a consortium comprised of the NIH Office of the Director and 14 NIH Institutes and Centers (ICs) that support neuroscience research. BPN provides neuroscience researchers with funding and access to a full range of industry-style drug development services and expertise.

The program, originally focused on small molecules, was launched for projects requiring medicinal chemistry optimization, PK, PD, drug manufacturing and formulation, investigational new drug (IND)-enabling toxicological studies support through Phase I clinical testing and it is now being expanded to include the development of biological therapeutics for neurological diseases (BPN-Biologics).

(https://neuroscienceblueprint.nih.gov/neurotherapeutics/bpn-biologics).

The URGenT program (https://www.ninds.nih.gov/Current-Research/Research-Funded- NINDS/Translational-Research/urgent-network) has been established by the NINDS to support the development and clinical evaluation of therapeutics to address ultra-rare genetically based neurological disorders. The network will provide neuroscience researchers with funding and access to a full range of industry-style biologics development services and expertise and in the future may expand to include other NIH institutes. The program is intended to rapidly advance patient-customized therapeutics through manufacturing, preclinical toxicology testing, and evaluation in Phase 1 clinical studies.

The HEAL-PTDP program (https://heal.nih.gov/) is a multi-IC initiative that has been established by the NIH to support preclinical optimization and development of safe, effective, and non- addictive biologic therapeutics to treat pain. The goal of the program is to accelerate the optimization and development of promising small molecule and biologic hits/leads to Phase I clinical trials and readiness for the Early Phase Pain Investigation Clinical Network (EPPIC-Net) or other Phase II clinical studies. Applicants must have a promising biologic hit/lead, robust biological rationale for the intended approach, and identified assays for optimization of the agent. The scope of this program includes optimization and early development activities, IND- enabling studies, development of a PD/ target engagement biomarker, assembly and filing of an IND application and Phase I clinical testing. This is a milestone-driven phased cooperative agreement program involving participation of NIH program staff in the development of the project plan and monitoring of research progress.

Additionally, NINDS has two (2) major Intramural Research Divisions with 52 labs that may require Biologics subject matter expertise.

The NINDS intramural divisions include:

1) The Basic Neuroscience Program (BNP), which pursues an understanding of the normal and abnormal structure and activities of the human research system.

2) The Clinical Neuroscience Program (CNP), which applies directly to disease detection, prevention, and treatment.

NINDS assesses and evolves the programs it supports over time, and consultants may be asked to support new Biologics drug discovery and development programs as needed across the period of performance in this contract. In all cases, the program would involve Biologics drug discovery and development to fall under the scope described here.

The NINDS anticipates needing 1-2 vendors with a broad array of subject matter experts available to support active and future Biologics drug discovery and development projects.

1.0 PERIOD OF PERFORMANCE

The total period of performance (PoP) includes a one-year base period and two (3) subsequent one-year option periods. The anticipated PoP dates are as follows:

Base Period: April 1, 2025 – March 30, 2026 Option Period One: April 1, 2026 – March 30, 2027 Option Period Two: April 1, 2027 – March 30, 2028

PLACE OF PERFORMANCE

The primary place of performance will be the Contractor site. Conference calls and email will be the primary mode of communication; however, the Contractor may be required to work at Government facilities or the facilities of selected principal investigators or contract research organizations (CROs) on an as needed basis.

Specific Requirements

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities not otherwise provided by the Government that are needed to support NIH biologics programs, including NIH BPN-Biologics, URGenT, HEAL PTDP, and NINDS Intramural labs.

Subject Matter Expert (SME) Consulting Services

The NINDS has regular needs for expert consultants in specific areas as different projects join the NINDS product discovery and development pipeline. Programs supported by these experts include all NINDS Intramural programs, NINDS Extramural programs, and trans-NIH efforts such as Helping End Addiction Long-Term (HEAL), Brain Research Through Advancing Innovative Neurotechnology (BRAIN), Blueprint Neurotherapeutics (BPN) Small Molecules, BPN Biologics, and Ultra-rare Gene-based Therapy (URGenT).

The Contractor shall provide this support on an ad hoc basis or while serving on NIH Biologics Lead Development Teams (LDTs) or URGENT Multi-Disciplinary Project Teams (MPTs) which include both SME consultants and NIH staff. These teams will map out a product development and clinical evaluation research strategy, including milestones, and oversee manufacturing and nonclinical study services by CROs.

SME consultants will be expected to provide feedback and guidance on project milestones, development strategy, study design, and data interpretation through in-person meetings, conference calls, and email. Specific consulting responsibilities will depend on the expertise of the individual consultant and the needs of individual biologics projects and programs. Consultants may be involved in multiple projects.

SMEs will be required on a part-time basis; hours will vary depending on the needs of the projects to which they are assigned. The NIH estimates 20-405 hours per year per SME.

The broad areas requiring SMEs include, but are not limited to, chemistry, controls, and manufacturing (CMC), pharmacokinetics/pharmacodynamics (PK/PD), absorption, distribution, metabolism, and excretion (ADME), toxicology, assay development, regulatory affairs, medical writing, biostatistics, quality assurance, and first-in-human study planning and design. These areas of expertise can be in all Biologics modalities and cell and gene therapy. Consultants in all areas are expected to:

1) Serve as the expert in their area to identify potential product development challenges and suggest strategies to address these challenges, provide expert advice in their area of expertise on study designs and approaches for product development, serve as a resource for requirements in their area of expertise (e.g., requirements for bioassay development, characterization of quality attributes for release testing, etc), assist in developing endpoints and milestones for projects, provide expert advice on necessary activities from the preclinical stage through the initial clinical stage (including medical writing and regulatory submission requirements), provide feedback on the potential tractability of a proposed product in the market.

2) Review and provide feedback on methods, reports, regulatory filings, milestones, study protocols, standard operating procedures, statistical analysis plans, statistical analysis results, and site audits in their area of expertise.

3) Collaborate in designing investigative studies in support of therapeutics development projects, including manufacturing and preclinical testing studies, collaborate in designing investigative new drug (IND)-enabling experiments, develop or collaborate in developing regulatory submissions and materials for regulatory agency meetings, prepare for and run regulatory agency meetings, develop statistical analysis plans, and develop and explain statistical analysis protocols and contingencies.

4) Assist in analyzing, interpreting, and evaluating data in their area of expertise for quality assurance checks, deviation assessments, and study results. These evaluations may be written or communicated in meetings.

5) Accompany NIH staff in visiting contract research organizations (CROs) and contract manufacturing organizations (CMOs) under contract to the NIH. Assist in inspecting facilities and discussing appropriateness of facilities and proposed methodology.

6) In partnership with other consultants, contractors, and the NIH staff, advise, strategically plan, and manage preclinical evaluation and safety testing, and IND submission and provide strategic guidance for the continued development and improvement of the NIH therapeutic development programs.

7) Facilitate discussions at all meetings and via email related to their area of expertise.

All SMEs are expected to meet the following criteria and demonstrate how they meet these criteria:

1) Knowledge of drug discovery and development process.

a. Demonstrated senior-level oversight of research and development efforts for therapeutic products

b. Broad experience across the entire biologics discovery and development process is especially desired.

c. Have managed a portfolio of comprehensive, milestone-driven pre-clinical drug development biologics-based therapeutics projects; planned, organized and directed inter-disciplinary drug research or development team efforts; developed policies, program directions, and procedures surrounding the administration of drug research programs.

d. Managed milestone-driven research and development projects in the area of biologics-based therapeutics, which require well-defined goals and objectives achieved with greatest efficiency. Developed and implemented quantitative and qualitative reviews of milestones to determine if they appropriately translated into accelerated progress of therapeutic candidates toward Investigational New Drug (IND) applications to the FDA, and provided clear indicators of a project's continued success or emergent difficulties.

e. Managed a portfolio of preclinical drug discovery and development projects (e.g., cooperative agreements) in the area of biologics-based therapeutics (including but not limited to e.g. peptides, proteins, antibodies, oligonucleotides, gene and cell therapies) with responsibility for all aspects of administration (i.e., organizing and managing).

Secured and implemented scientific advice from senior leaders and colleagues and applied drug discovery and development expertise.

2) Ability to analyze and evaluate milestones to manage a drug development program.

a. Developed project plans and associated communications documents. Managed the day-to-day activities of assigned Programs and Projects; directed and managed project development from beginning to end; and estimated the resources needed to achieve Program and Project goals. Managed key relationships internal and external to an organization.

b. Reviewed, analyzed, and evaluated pre-clinical drug development data

c. Provided an in-depth review, analysis, evaluation, and recommendation of milestones at the beginning of a funding year or funding cycle (depending on the Program or Project) to support a determination as to whether a project should be continued. This in-depth review included assessment and recommendations to ensure that individual projects were competitively evaluated against the broader research landscape.

3) Skill in applying Project Management tools to manage drug discovery and development programs.

a. Ensured that projects were managed and executed in line with the rules and governance of an organization and cognizant regulating bodies.

b. Prepared a variety of routine and special reports as requested by senior management.

Researched and prepared reports, briefing materials, and other compilations of Program and Project activities and policies for use in policy development, program planning, evaluation and implementation, and presentation to senior advisors. Researched and wrote scientific review presentations, position papers, talking point papers, and briefing materials for senior staff as requested.

c. Has a track-record of successfully building and leading product development teams

d. Defined project objectives; planned, executed, and finalized projects according to strict deadlines and within budget; oversaw quality control, assembled data, and managed program budgets.

4) Ability to communicate clearly, logically and persuasively on complex scientific issues.

a. Has attended and presented drug research findings at conferences and meetings with high ranking scientists in academia, industry, or government.

b. Developed and delivered progress reports, proposals, requirements documentation, and presentations.

c. Has built, developed, and grown relationships vital to the success of a Program or

Project to establish worldwide collaborative relationships among government, academia, and industry that are focused on the search for therapeutic interventions and treatments for neurological disorders.

d. Has experience in team leadership, consulting, or service on strategic and advisory boards .

e. A significant track-record of scientific accomplishment as evidenced by publications and/or contributions to the development of marketed products.

f. Must be able to work in a virtual, cross-functional team environment and manage competing priorities.

g. Must participate actively in project team discussions.

h. Must have strong interpersonal skills, attention to detail, excellent organizational, writing, communication, presentation, and documentation skills as well as computer and software literacy.

i. Must have experience working with multi-disciplinary teams at a senior level preferably in the biopharmaceutical industry, especially teams with members from outside organizations and members at various management levels.

Education and Specific Work Experience

a) A MS, PhD, or MD in a relevant scientific discipline is preferred. A candidate without a PhD should have equivalent experience.

b) Must have at least 10 years of relevant professional experience

c) Must have at least 10 years demonstrated experience in product development

d) Must have at least 10 years of experience in managing or being a senior leader in product development projects in the biopharmaceutical industry

e) SMEs supporting the URGenT program must also have at least 5 years of experience in supporting rare and/or ultra-rare biologics product development programs, including modalities such as gene therapy and/or oligonucleotides.

f) SMEs supporting BPN-Biologics must have at least 10 years of experience across broad biological therapeutics product development programs, including but not limited to proteins, peptides, antibodies, oligonucleotides, cellular therapy, gene therapy, and/or immunotherapy

g) Experience with product development for nervous system conditions is preferred but not required

h) Experience interacting with the FDA or other regulatory authorities preferred

i) Extensive understanding of FDA or other regulatory agency requirements for IND submissions and clinical trial execution (and when applicable for ultra-rare diseases) is preferred

2.0 DELIVERABLES AND REPORTING REQUIREMENTS

SME consultants shall be responsible for providing subject matter expertise in the following areas:

1) Needs and/or gap assessment of ultra-rare gene-based therapeutic development processes

2) Advice on technical flow of various stages of the development process

3) Estimation of time, cost, and effort involved in each stage of the development process

Consultants shall also be responsible for submitting ad hoc summary reports of their analyses as needed.

3.0 OTHER CONSIDERATIONS

3.1 Key Personnel

The Contractor shall establish a single point-of-contact to be considered Key Personnel and to assist with bringing SMEs onto projects as needed. The SMEs working on active projects will be added as Key Personnel to the contract when they begin work on a project.

3.2 Government-furnished Equipment

The Government does not anticipate providing Government-furnished property. Project related data (i.e., Government furnished information) will be provided to the Contractor for performance of work efforts. All data provided to the Contractor must be treated as confidential and shall not be disclosed to any third party.

Project data will be collected and stored by the NIH. NIH will provide data as needed to the Contractor each time it requests service. The Contractor may store data up to 12 months after initially receiving it, after which time the Contractor should either delete the data files and sanitize the computer using National Institute of Standards and Technology (NIST) SP 800-88 (current revision), or if information is still needed, contact the COR for permission to store the data for a longer period of time.

3.3 Travel

The Contractor may be required to travel within the contiguous United States to provide the services described in this SOW. The Contractor shall make its own travel arrangements; the Government shall reimburse all reasonable travel costs up to the Government approved limits.

All travel arrangements must be made in accordance with Federal Travel Regulations in effect at the time of travel and must be approved by the Contracting Officer’s Representative and authorized by the Contracting Officer prior to being finalized or invoiced.

Optional travel will include up to six (6) trips per year on this contract, with a per trip cost of $1,200. An annual A Not to Exceed (NTE) amount of $7,200 for travel costs shall be exercised, if needed, using FAR Clause 52.217-7 Option for Increased Quantity-Separately Priced Line Item.

3.4 Information System Security Plan

The Contractor must ensure that any computer system used in the course of this contract shall include the following features:

3.4.1 Any computer used in relation to this contract must be patched with most updated IT Security Patches.

3.4.2 Any Contractor computer used in relation this contract must have virus protection loaded and running with definition files that are updated on at least a daily basis.

3.4.3 Hard drives and portable media used for this contract must be encrypted using the FIPS 140-2 standard.

3.4.4 Contractors are required to take NIH Security and Privacy Training annually http://irtsectraining.nih.gov/

3.4.5 Contractor are required to sign the NIH non-disclosure agreement http://irtsectraining.nih.gov/NIH_Non-Disclosure_Agreement.pdf

3.4.6 Contractors are required to report any lost or stolen NIH data to the NINDS ISSO within one hour of knowing of the lost or theft even if the data is on a Contractor furnished computer.

3.4.7 Contractors are required to adhere to the NIH IT rules of behavior which can be found at https://ocio.nih.gov/InfoSecurity/training/Pages/nihitrob.aspx

3.4.8 Any computers used in reference to this contract must be assessed for vulnerabilities.

3.4.9 Any computers used in reference to this contract must be backed up on an external hard drive which is password protected.

3.4.10 Any computers used in reference to this contract must have auditing enabled such that if an incident occurred then that event could be reconstructed.

3.4.11 Any computers that are used in reference to this contract must employ at a minimum username and password authentication or if possible two factor authentication.

3.4.12 Any computer used in relation to this contract must be password protected. All

Password must meet the NIH standard such that users must choose passwords that have at least eight characters and at least three of the following types of characters:

3.4.12.1 capital letters

3.4.12.2 lower case letters

3.4.12.3 numeric characters

3.4.12.4 special characters (!@#$%^&*()_+|~-=\`{}[]:";'<>?,./)

3.5 Data Rights

The NIH shall have unlimited rights to, and ownership of, all deliverables provided under this contract, including reports, analyses, recommendations and all other deliverables. This also includes any additional deliverables required by contract change. The definition of “unlimited rights” is contained in Federal Acquisition Regulation (FAR) 27.401, “Definitions.” FAR clause 52.227-14, “Rights General,” shall be incorporated by reference into any resulting award.

Project related data will be provided to the Contractor for performance of work efforts. All data provided to the Contractor must be treated as confidential and shall not be disclosed to any third party.

3.6 Section 508 – Electronic Information Technology Standards

Section 508 of the Rehabilitation Act of 1973 requires that Federal agencies’ electronic and information technology (EIT) is accessible to people with disabilities. The Federal Acquisition Regulations (FAR) Final Rule for Section 508 (EIT Accessibility) can be found at www.section508.gov and at the Access Board’s Web site at https://www.access- board.gov/508.htm.

The contractor must state that they will comply with the requirements of Section 508 or cite a justifiable reason for an exception.

3.7 Confidentiality of Information

Consultant(s) may only disclose the information/data generated for a particular project to other participants on that same project. These specific individuals will be identified when the consultant is http://irtsectraining.nih.gov/ http://irtsectraining.nih.gov/NIH_Non-Disclosure_Agreement.pdf https://ocio.nih.gov/InfoSecurity/training/Pages/nihitrob.aspx assigned to a project. Consultant(s) shall guarantee strict confidentiality of the information/data that is provided by the NINDS or by any other participant on a project to which the consultant is assigned. The NINDS has determined that the information/data that the consultant will be provided during the performance of the consulting contract is of a sensitive nature.

Disclosure of the information/data, in whole or in part, by the consultant to anyone else can only be made after the consultant receives prior written approval from the Contracting Officer.

Whenever the consultant is uncertain with regard to the proper handling of information/data under the contract, the consultant shall obtain a written determination from the Contracting Officer.

Contractor agrees that it will not use the Confidential Information for any purpose except as set forth within this SOW, unless such time as such Confidential Information becomes public information.

3.8 Publications and Publicity

Not applicable. The Contractor will not write or publish articles of data produced as a result of the SOW requirements.

3.9 Non-Personal Services Statement

Contract employee performing services will be controlled, directed, and supervised at all times by management personnel of the contractor. Actions of contractor employees may not be interpreted or implemented in any manner that results in any contractor employee creating or modifying Federal policy, obligating the appropriated funds of the U.S. Government, overseeing the work of Federal employees, providing direct personal services to any Federal employee or otherwise violating the prohibitions set forth in Parts 7.5 and 37.1 of the Federal Acquisition Regulations (FAR).

Education and Specific Work Experience